المؤلفون: Kristina O. Smiley, Hollian R. Phillipps, Chenyun Fang, Rosemary S. E. Brown, David R. Grattan

المصدر: Frontiers in Behavioral Neuroscience, Vol 17 (2023)

مصطلحات موضوعية: prolactin, neurogenesis, mating, paternal behavior, male mice C57BL, infanticide, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: Parenting involves major behavioral transitions that are supported by coordinated neuroendocrine and physiological changes to promote the onset of novel offspring-directed behaviors. In comparison to maternal care, however, the mechanisms underlying the transition to paternal care are less understood. Male laboratory mice are predominantly infanticidal as virgins but show paternal responses 2 weeks after mating. Interestingly, males show a mating-induced surge of prolactin, which we hypothesized may be involved in initiating this behavioral transition. During pregnancy, prolactin stimulates olfactory bulb neurogenesis, which is essential for maternal behavior. Mating induces olfactory bulb neurogenesis in males, but it is unknown whether this is driven by prolactin or is important for subsequent paternal care. New olfactory neurons are generated from cells in the subventricular zone (SVZ) and take about 2 weeks to migrate to the olfactory bulb, which may account for the delayed behavioral change in mated males. We investigated whether mating increases cell proliferation at the SVZ. Males were either mated, exposed to receptive female cues, or left alone (control) and injected with Bromodeoxyuridine (BrdU, a marker of cell division). Contrary to our hypothesis, we found that mating decreased cell proliferation in the caudal lateral portion of the SVZ. Next, we tested whether prolactin itself mediates cell proliferation in the SVZ and/or new cell survival in the olfactory bulb by administering bromocriptine (prolactin inhibitor), vehicle, or bromocriptine + prolactin prior to mating. While suppressing prolactin had no effect on cell proliferation in the SVZ, administering exogenous prolactin resulted in significantly higher BrdU-labeled cells in mated but not virgin male mice. No effects of prolactin were observed on new olfactory cell survival. Taken together, prolactin may have context-dependent effects on new cell division in the SVZ, while other unknown mechanisms may be driving the effects on new olfactory cell survival following mating.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fnbeh.2023.1227726/fullTest; https://doaj.org/toc/1662-5153Test

الوصول الحر: https://doaj.org/article/b294ec205ac14e1595e04762301ebb87Test

المؤلفون: Vincent Goffin, Damasia Becu-Villalobos, Vera Popovic, David R. Grattan

المصدر: Frontiers in Endocrinology, Vol 14 (2023)

مصطلحات موضوعية: prolactin, disease, cancer, metabolism, inflammation, pituitary, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fendo.2023.1213895/fullTest; https://doaj.org/toc/1664-2392Test

الوصول الحر: https://doaj.org/article/56c28fcff37d4353bb55d1a2cca71d54Test

المؤلفون: Kelly C. Radecki, Matthew J. Ford, Hollian R. Phillipps, Mary Y. Lorenson, David R. Grattan, Yojiro Yamanaka, Ameae M. Walker

المصدر: FASEB BioAdvances, Vol 4, Iss 7, Pp 485-504 (2022)

مصطلحات موضوعية: cilia, estrous cycle, gene expression profiling, hyperprolactinemia, prolactin, receptors, Biology (General), QH301-705.5

الوصف: Abstract Little is known about the physiological role of prolactin in the oviduct. Examining mRNA for all four isoforms of the prolactin receptor (PRLR) in mice by functional oviduct segment and stage of the estrous cycle, we found short form 3 (SF3) to be the most highly expressed, far exceeding the long form (LF) in highly ciliated areas such as the infundibulum, whereas in areas of low ciliation, the SF3 to LF ratio was ~1. SF2 expression was low throughout the oviduct, and SF1 was undetectable. Only in the infundibulum did PRLR ratios change with the estrous cycle. Immunofluorescent localization of SF3 and LF showed an epithelial (both mucosal and mesothelial) distribution aligned with the mRNA results. Despite the high SF3/LF ratio in densely ciliated regions, these regions responded to an acute elevation of prolactin (30 min, intraperitoneal), with LF‐tyrosine phosphorylated STAT5 seen within cilia. Collectively, these results show ciliated cells are responsive to prolactin and suggest that prolactin regulates estrous cyclic changes in ciliated cell function in the infundibulum. Changes in gene expression in the infundibulum after prolonged prolactin treatment (7‐day) showed prolactin‐induced downregulation of genes necessary for cilium development/function, a result supporting localization of PRLRs on ciliated cells, and one further suggesting hyperprolactinemia would negatively impact ciliated cell function and therefore fertility. Flow cytometry, single‐cell RNAseq, and analysis of LF‐td‐Tomato transgenic mice supported expression of PRLRs in at least a proportion of epithelial cells while also hinting at additional roles for prolactin in smooth muscle and other stromal cells.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2573-9832Test

الوصول الحر: https://doaj.org/article/091ce3c1e9ae4ed4b554afcaf7359675Test

المؤلفون: Muhammad Hassan, David R. Grattan, Beulah Leitch

المصدر: Biomolecules, Vol 13, Iss 1, p 186 (2023)

مصطلحات موضوعية: GABAA receptor, cortico-thalamocortical network, absence epilepsy, absence seizures, primary somatosensory cortex, stargazer mouse, Microbiology, QR1-502

الوصف: Childhood absence epilepsy seizures arise in the cortico-thalamocortical network due to multiple cellular and molecular mechanisms, which are still under investigation. Understanding the precise mechanisms is imperative given that treatment fails in ~30% of patients while adverse neurological sequelae remain common. Impaired GABAergic neurotransmission is commonly reported in research models investigating these mechanisms. Recently, we reported a region-specific reduction in the whole-tissue and synaptic GABAA receptor (GABAAR) α1 subunit and an increase in whole-tissue GAD65 in the primary somatosensory cortex (SoCx) of the adult epileptic stargazer mouse compared with its non-epileptic (NE) littermate. The current study investigated whether these changes occurred prior to the onset of seizures on postnatal days (PN) 17–18, suggesting a causative role. Synaptic and cytosolic fractions were biochemically isolated from primary SoCx lysates followed by semiquantitative Western blot analyses for GABAAR α1 and GAD65. We found no significant changes in synaptic GABAAR α1 and cytosolic GAD65 in the primary SoCx of the stargazer mice at the critical developmental stages of PN 7–9, 13–15, and 17–18. This indicates that altered levels of GABAAR α1 and GAD65 in adult mice do not directly contribute to the initial onset of absence seizures but are a later consequence of seizure activity.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2218-273X/13/1/186Test; https://doaj.org/toc/2218-273XTest

الوصول الحر: https://doaj.org/article/8478c7356b774b3babcad2e0d58d2fdaTest

المؤلفون: Teodora Georgescu, Judith M. Swart, David R. Grattan, Rosemary S. E. Brown

المصدر: Frontiers in Global Women's Health, Vol 2 (2021)

مصطلحات موضوعية: prolactin, placental lactogen (PL), prolactin receptor, maternal behavior, maternal mood, neuroendocrinology, Gynecology and obstetrics, RG1-991, Women. Feminism, HQ1101-2030.7

الوصف: Transition into motherhood involves profound physiological and behavioral adaptations that ensure the healthy development of offspring while maintaining maternal health. Dynamic fluctuations in key hormones during pregnancy and lactation induce these maternal adaptations by acting on neural circuits in the brain. Amongst these hormonal changes, lactogenic hormones (e.g., prolactin and its pregnancy-specific homolog, placental lactogen) are important regulators of these processes, and their receptors are located in key brain regions controlling emotional behaviors and maternal responses. With pregnancy and lactation also being associated with a marked elevation in the risk of developing mood disorders, it is important to understand how hormones are normally regulating mood and behavior during this time. It seems likely that pathological changes in mood could result from aberrant expression of these hormone-induced behavioral responses. Maternal mental health problems during pregnancy and the postpartum period represent a major barrier in developing healthy mother-infant interactions which are crucial for the child's development. In this review, we will examine the role lactogenic hormones play in driving a range of specific maternal behaviors, including motivation, protectiveness, and mother-pup interactions. Understanding how these hormones collectively act in a mother's brain to promote nurturing behaviors toward offspring will ultimately assist in treatment development and contribute to safeguarding a successful pregnancy.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fgwh.2021.767467/fullTest; https://doaj.org/toc/2673-5059Test

الوصول الحر: https://doaj.org/article/d7eb26ed4653465a81da9652135a7867Test

المؤلفون: Zin Khant Aung, Ilona C. Kokay, David R. Grattan, Sharon R. Ladyman

المصدر: Frontiers in Endocrinology, Vol 12 (2021)

مصطلحات موضوعية: prolactin, pregnancy, beta-cell, hypothalamus, prolactin receptor, gestation, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: Adaptive changes in glucose homeostasis during pregnancy require proliferation of insulin-secreting beta-cells in the pancreas, together with increased sensitivity for glucose-stimulated insulin secretion. Increased concentrations of maternal prolactin/placental lactogen contribute to these changes, but the site of action remains uncertain. Use of Cre-lox technology has generated pancreas-specific prolactin receptor (Prlr) knockouts that demonstrate the development of a gestational diabetic like state. However, many Cre-lines for the pancreas also express Cre in the hypothalamus and prolactin could act centrally to modulate glucose homeostasis. The aim of the current study was to examine the relative contribution of prolactin action in the pancreas and brain to these pregnancy-induced adaptations in glucose regulation. Deletion of prolactin receptor (Prlr) from the pancreas using Pdx-cre or Rip-cre led to impaired glucose tolerance and increased non-fasting blood glucose levels during pregnancy. Prlrlox/lox/Pdx-Cre mice also had impaired glucose-stimulated insulin secretion and attenuated pregnancy-induced increase in beta-cell fraction. Varying degrees of Prlr recombination in the hypothalamus with these Cre lines left open the possibility that central actions of prolactin could contribute to the pregnancy-induced changes in glucose homeostasis. Targeted deletion of Prlr specifically from the forebrain, including areas of expression induced by Pdx-Cre and Rip-cre, had no effect on pregnancy-induced adaptations in glucose homeostasis. These data emphasize the pancreas as the direct target of prolactin/placental lactogen action in driving adaptive changes in glucose homeostasis during pregnancy.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fendo.2021.765976/fullTest; https://doaj.org/toc/1664-2392Test

الوصول الحر: https://doaj.org/article/5fd72de4ea9e4462a13638d7b474802eTest

المؤلفون: Siew H. Yip, Nicola Romanò, Papillon Gustafson, David J. Hodson, Eloise J. Williams, Ilona C. Kokay, Agnes O. Martin, Patrice Mollard, David R. Grattan, Stephen J. Bunn

المصدر: Cell Reports, Vol 26, Iss 7, Pp 1787-1799.e5 (2019)

مصطلحات موضوعية: Biology (General), QH301-705.5

الوصف: Summary: Altered physiological states require neuronal adaptation. In late pregnancy and lactation, a sub-population of the mouse hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons alters their behavior to synthesize and release met-enkephalin rather than dopamine. These neurons normally release dopamine to inhibit prolactin secretion and are activated by prolactin in a short-loop feedback manner. In lactation, dopamine synthesis is suppressed in an opioid-dependent (naloxone-reversible) manner, meaning that prolactin secretion is disinhibited. Conditional deletion of the prolactin receptor in neurons reveals that this change in phenotype appears to be driven by prolactin itself, apparently through an alteration in intracellular signaling downstream of the prolactin receptor that favors enkephalin production instead of dopamine. Thus, prolactin effectively facilitates its own secretion, which is essential for lactation and maternal behavior. These studies provide evidence of a physiologically important, reversible alteration in the behavior of a specific population of hypothalamic neurons in the adult brain. : Pituitary prolactin secretion is inhibited by dopamine released by hypothalamic neurons. Yip et al. show that, during lactation, these TIDA neurons alter their response to prolactin and release enkephalin in place of dopamine. This mechanism promotes rather than inhibits prolactin secretion, supporting its elevation during lactation. Keywords: prolactin, prolactin receptor, dopamine, encephalin, hypothalamus, tuberoinfundibular dopaminergic neurons, neuronal plasticity, lactation, lactotrophs

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2211124719300968Test; https://doaj.org/toc/2211-1247Test

الوصول الحر: https://doaj.org/article/b51f192b751d40d8aa8149ff8186f354Test

المؤلفون: Zane B. Andrews, Hua Zhao, Tony Frugier, Reiko Meguro, David R. Grattan, Kyoko Koishi, Ian S. McLennan

المصدر: Neurobiology of Disease, Vol 21, Iss 3, Pp 568-575 (2006)

مصطلحات موضوعية: Parkinson's disease, Dopamine, DOPAC, TGF-β2, Substantia nigra, Susceptibility genes, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: The transforming growth factor-betas (TGF-βs) regulate the induction of dopaminergic neurons and are elevated in the CSF of Parkinson's patients. We report here that mice with TGF-β2 haploinsufficiency (TGF-β2+/−) have subclinical defects in the dopaminergic neurons of their substantia nigra pars compacta. At 6 weeks of age, the TGF-β2+/− mice had 12% fewer dopaminergic neurons than wild-type littermates. No additional loss of neurons occurred during the next 5 months, although striatal dopamine declined to 70% of normal. The level of 3,4-dihydroxphenylacetic acid was normal in the TGF-β2+/− mice, indicating that a compensatory mechanism maintains dopamine stimulation of their striatum. The TGF-β2+/− mice had normal sensitivity to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tretrahydropyridine, despite having reduced levels of monoamine oxidase-B. These results raise the possibility that people with naturally low levels of TGF-β2 may have less functional reserve in their nigrostriatal pathway, causing them to be at increased risk of developing Parkinson disease.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S0969996105002457Test; https://doaj.org/toc/1095-953XTest

الوصول الحر: https://doaj.org/article/0807abedc9e24733a92bc715dd3e1f93Test

المؤلفون: Chris S. Booker, David R. Grattan

المصدر: PeerJ, Vol 2, p e560 (2014)

مصطلحات موضوعية: Interleukin-18, Toll-like receptor, Splice variant, Comparative genomics, Medicine, Biology (General), QH301-705.5

الوصف: Interleukin-18 (IL-18) is a pro-inflammatory cytokine which stimulates activation of the nuclear factor kappa beta (NF-κB) pathway via interaction with the IL-18 receptor. The receptor itself is formed from a dimer of two subunits, with the ligand-binding IL-18Rα subunit being encoded by the IL18R1 gene. A splice variant of murine IL18r1, which has been previously described, is formed by transcription of an unspliced intron (forming a ‘type II’ IL18r1 transcript) and is predicted to encode a receptor with a truncated intracellular domain lacking the capacity to generate downstream signalling. In order to examine the relevance of this finding to human IL-18 function, we assessed the presence of a homologous transcript by reverse transcription-polymerase chain reaction (RT-PCR) in the human and rat as another common laboratory animal. We present evidence for type II IL18R1 transcripts in both species. While the mouse and rat transcripts are predicted to encode a truncated receptor with a novel 5 amino acid C-terminal domain, the human sequence is predicted to encode a truncated protein with a novel 22 amino acid sequence bearing resemblance to the ‘Box 1’ motif of the Toll/interleukin-1 receptor (TIR) domain, in a similar fashion to the inhibitory interleukin-1 receptor 2. Given that transcripts from these three species are all formed by inclusion of homologous unspliced intronic regions, an analysis of homologous introns across a wider array of 33 species with available IL18R1 gene records was performed, which suggests similar transcripts may encode truncated type II IL-18Rα subunits in other species. This splice variant may represent a conserved evolutionary mechanism for regulating IL-18 activity.

وصف الملف: electronic resource

العلاقة: https://peerj.com/articles/560.pdfTest; https://peerj.com/articles/560Test/; https://doaj.org/toc/2167-8359Test

الوصول الحر: https://doaj.org/article/1f47b545d1e649a2952ca84afd4eccb8Test

المؤلفون: David R. Grattan

المصدر: EBioMedicine, Vol 8, Iss C, Pp 26-27 (2016)

مصطلحات موضوعية: Medicine, Medicine (General), R5-920

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2352396416302249Test; https://doaj.org/toc/2352-3964Test

الوصول الحر: https://doaj.org/article/1719e6e4e7f94d24a47a86204d830d54Test